Kiho Im

Brain Size and Cortical Structure in the Adult Human Brain

We investigated the scale relationship between size and cortical structure of human brains in a large sample of magnetic resonance imaging data. Cortical structure was estimated with several measures (cortical volume, surface area, and thickness, sulcal depth, and absolute mean curvature in sulcal regions and sulcal walls) using three-dimensional surface-based methods in 148 normal subjects (n [men/women]: 83/65, age [mean +/- standard deviation]: 25.0 +/- 4.9 years). We found significantly larger scaling exponents than geometrically predicted for cortical surface area, absolute mean curvature in sulcal regions and in sulcal walls, and smaller ones for cortical volume and thickness. As brain size increases, the cortex thickens only slightly, but the degree of sulcal convolution increases dramatically, indicating that human cortices are not simply scaled versions of one another. Our results are consistent with previous hypotheses that greater local clustering of interneuronal connections would be required in a larger brain, and fiber tension between local cortical areas would induce cortical folds. We suggest that sex effects are explained by brain size effects in cortical structure at a macroscopic and lobar regional level, and that it is necessary to consider true relationships between cortical measures and brain size due to the limitations of linear stereotaxic normalization.

Gender difference analysis of cortical thickness in healthy young adults with surface-based methods.

We have examined gender differences of cortical thickness using a 3-D surface-based method that enables more accurate measurement in deep sulci and localized regional mapping compared to volumetric analyses. Cortical thickness was measured using a direct method for calculating the distance between corresponding vertices from inner and outer cortical surfaces. We normalized cortical surfaces using 2-D surface registration and performed diffusion smoothing to reduce the variability of folding patterns and to increase the power of the statistical analysis. In stereotaxic space, significant localized cortical thickening in women was found extensively in frontal, parietal and occipital lobes, including the superior frontal gyrus (SFG), superior parietal gyrus (SPG), inferior frontal gyrus (IFG) and postcentral gyrus (PoCG) in the left hemisphere and mostly in the parietal lobe, including the SPG in the right hemisphere. In the temporal lobe, small regions of the left and right caudal superior temporal gyrus (STG) and the left temporal pole showed significantly greater cortical thickness in women. The temporal lobe shows relatively less significant thickening than other lobes in both hemispheres. In native space, significantly greater cortical thickness in women was detected in left parietal region, including SPG and PoCG. No significant local increases of cortical thickness were observed in men in both spaces. These findings suggest statistically significant cortical thickening in women in localized anatomical regions, which is consistent with several previous studies and may support a hypothesis of sexual dimorphism.

Cortical thickness in single- versus multiple-domain amnestic mild cognitive impairment

Amnestic mild cognitive impairment (aMCI) can be classified into single domain (S-aMCI) and multiple domain (M-aMCI) subtypes. However, there have been no studies that specifically investigate the structural differences that support this classification. In an attempt to compare regional cortical thickness in two subtypes of aMCI, we aimed to map the distribution of cortical thinning using a surface based cortical analysis of magnetic resonance imaging. The cortical thickness across the entire brain was measured in 9 patients with S-aMCI, 22 patients with M-aMCI, and 61 normal healthy subjects. Differences in the patterns of cortical thinning between S-aMCI and M-aMCI were assessed using ANCOVA on a vertex-by-vertex basis, and statistical maps of differences in cortical thickness between the groups were constructed using a surface model. Relative to controls, S-aMCI patients showed cortical thinning in the left medial temporal lobe, and M-aMCI patients showed cortical thinning in the left medial temporal lobe, precuneus, and anterior and inferior basal temporal, insular, and temporal association cortices. When the two MCI groups were directly compared, M-aMCI patients showed cortical thinning in left precuneus. Our studies suggest that M-aMCI is a transitional state between S-aMCI and Alzheimers disease, and that the cortical thinning is evidence that the precuneus is responsible for the multiple cognitive impairments in M-aMCI.

Fractal dimension in human cortical surface: multiple regression analysis with cortical thickness, sulcal depth, and folding area.

Fractal dimension (FD) has been widely used to provide a quantitative description of structural complexity in the cerebral cortex. FD is an extremely compact measure of shape complexity, condensing all details into a single numeric value. We interpreted the variation of the FD in the cortical surface of normal controls through multiple regression analysis with cortical thickness, sulcal depth, and folding area related to cortical complexity. We used a cortical surface showing a reliable representation of folded gyri and manually parcellated it into frontal, parietal, temporal, and occipital regions for regional analysis. In both hemispheres the mean cortical thickness and folding area showed significant combination effects on cortical complexity and accounted for about 50% of its variance. The folding area was significant in accounting for the FD of the cortical surface, with positive coefficients in both hemispheres and several lobe regions, while sulcal depth was significant only in the left temporal region. The results may suggest that human cortex develops a complex structure through the thinning of cortical thickness and by increasing the frequency of folds and the convolution of gyral shape rather than by deepening sulcal regions. Through correlation analysis of FD with IQ and the number of years of education, the results showed that a complex shape of the cortical surface has a significant relationship with intelligence and education. Our findings may indicate the structural characteristics that are revealed in the cerebral cortex when the FD in human brain is increased, and provide important information about brain development. Hum Brain Mapp, 2006.

Evolutionarily Dynamic Alternative Splicing of GPR56 Regulates Regional Cerebral Cortical Patterning

Development of surface folds of the human brain is controlled in sections. [Also see Perspective by Rash and Rakic] The human neocortex has numerous specialized functional areas whose formation is poorly understood. Here, we describe a 15–base pair deletion mutation in a regulatory element of GPR56 that selectively disrupts human cortex surrounding the Sylvian fissure bilaterally including “Broca’s area,” the primary language area, by disrupting regional GPR56 expression and blocking RFX transcription factor binding. GPR56 encodes a heterotrimeric guanine nucleotide–binding protein (G protein)–coupled receptor required for normal cortical development and is expressed in cortical progenitor cells. GPR56 expression levels regulate progenitor proliferation. GPR56 splice forms are highly variable between mice and humans, and the regulatory element of gyrencephalic mammals directs restricted lateral cortical expression. Our data reveal a mechanism by which control of GPR56 expression pattern by multiple alternative promoters can influence stem cell proliferation, gyral patterning, and, potentially, neocortex evolution. Fine-Tuning Brain Gyrations A handful of patients who suffer from seizures and mild intellectual disability have now led the way to insights about how one piece of regulatory DNA controls development of a section of the human cortex. Imaging the brains of these patients, Bae et al. (p. 764; see the Perspective by Rash and Rakic) observed malformations on the surface folds in a brain region that includes “Brocas area,” the main region underlying language. The three affected families shared a 15–base pair deletion in the regulatory region of a gene, GPR56, which encodes a G protein–coupled receptor required for normal cortical development that is expressed in cortical progenitor cells.

Sulcal morphology changes and their relationship with cortical thickness and gyral white matter volume in mild cognitive impairment and Alzheimer's disease.

We investigated the changes of sulcal shape (average mean curvature in folded regions and sulcal depth) in mild cognitive impairment (MCI) and Alzheimers disease (AD) using quantitative surface-based methods in a large sample of magnetic resonance imaging data. Moreover, we observed their relationships with cortical thickness and gyral white matter (WM) volume, while considering age effect. This study involved 85 normal controls (n [men/women]: 36/49, age [mean+/-SD]: 71.1+/-4.9 years), and 100 MCI (44/56, 71.8+/-6.5) and 145 AD subjects (53/92, 72.7+/-7.3). We found significantly lower average mean curvature (greater sulcal widening) and shallower sulcal depth with disease progression from controls to MCI and MCI to AD. The most remarkable change in MCI and AD was sulcal widening observed in the temporal lobe (average mean curvature, control [mean]: 0.564, MCI: 0.534 (5.3% decrease from control), AD: 0.486 (13.8% and 9.0% decrease from control and MCI respectively)). Of the four measurements, the sulcal widening measurement showed the highest sensitivity in revealing group differences between control and MCI, which might be useful for detecting early dementia. Significant reductions in cortical thickness and gyral WM volume also occurred in MCI and AD. Multiple regression analysis demonstrated that a wider and shallower sulcal shape was primarily associated with decreased cortical thickness and gyral WM volume in each group. Age-related trends for the sulcal shape were not strongly found when cortical thickness and gyral WM volume were considered.

Spatial Distribution of Deep Sulcal Landmarks and Hemispherical Asymmetry on the Cortical Surface

The locally deepest regions of major sulci, the sulcal pits, are thought to be the first cortical folds to develop and are closely related to functional areas. We examined the spatial distribution of sulcal pits across the entire cortical region, and assessed the hemispheric asymmetry in their frequency and distribution in a large group of normal adult brains. We automatically extracted sulcal pits from magnetic resonance imaging data using surface-based methods and constructed a group map from 148 subjects. The spatial distribution of the sulcal pits was relatively invariant between individuals, showing high frequency and density in specific focal areas. The left and right sulcal pits were spatially covariant in the regions of the earliest developed sulci. The sulcal pits with great spatial invariance appear to be useful as stable anatomical landmarks. We showed the most significant asymmetry in the frequency and spatial variance of sulcal pits in the superior temporal sulcus, which might be related to the lateralization of language function to the left hemisphere, developing more consistently and strongly than for the right. Our analyses support previous empirical and theoretical studies, and provide additional insights concerning the anatomical and functional development of the brain.

Pattern classification using principal components of cortical thickness and its discriminative pattern in schizophrenia.

We proposed pattern classification based on principal components of cortical thickness between schizophrenic patients and healthy controls, which was trained using a leave-one-out cross-validation. The cortical thickness was measured by calculating the Euclidean distance between linked vertices on the inner and outer cortical surfaces. Principal component analysis was applied to each lobe for practical computational issues and stability of principal components. And, discriminative patterns derived at every vertex in the original feature space with respect to support vector machine were analyzed with definitive findings of brain abnormalities in schizophrenia for establishing practical confidence. It was simulated with 50 randomly selected validation set for the generalization and the average accuracy of classification was reported. This study showed that some principal components might be more useful than others for classification, but not necessarily matching the ordering of the variance amounts they explained. In particular, 40-70 principal components rearranged by a simple two-sample t-test which ranked the effectiveness of features were used for the best mean accuracy of simulated classification (frontal: (left(%)|right(%))=91.07|88.80, parietal: 91.40|91.53, temporal: 93.60|91.47, occipital: 88.80|91.60). And, discriminative power appeared more spatially diffused bilaterally in the several regions, especially precentral, postcentral, superior frontal and temporal, cingulate and parahippocampal gyri. Since our results of discriminative patterns derived from classifier were consistent with a previous morphological analysis of schizophrenia, it can be said that the cortical thickness is a reliable feature for pattern classification and the potential benefits of such diagnostic tools are enhanced by our finding.

Cortical Thinning in Vascular Mild Cognitive Impairment and Vascular Dementia of Subcortical Type

Amnestic mild cognitive impairment (MCI) is known to be a preclinical stage of Alzheimers disease (AD). Similarly, MCI associated with small‐vessel disease (svMCI), might be a forme froste of subcortical vascular dementia (SVaD). Patterns of cortical thinning in addition to the ischemia rating on MRI may further elucidate the clinical characteristics and pathogenesis of SVaD and svMCI. We tried to determine if svMCI differs from SVaD in the distribution of cortical atrophy, which may help understand the hierarchy between svMCI and SVaD and possibly also how svMCI evolves into SVaD.

Cortical thinning related to periventricular and deep white matter hyperintensities

Previous studies showed that white matter hyperintensities (WMH) are related to cognitive decline in patients with mild cognitive impairment (MCI) or dementia. Moreover, periventricular WMH (periventricular white matter hyperintensities (PWMH)) and deep WMH (deep white matter hyperintensities (DWMH)) may have different effects on cognition. The purpose of this study is to investigate the contributions of PWMH and DWMH to the topography of cortical thinning and to investigate the relationship among WMH, cortical thinning, and cognitive impairments. Participants included 226 patients with Alzheimers disease or subcortical vascular dementia, and 135 patients with amnestic MCI or subcortical vascular MCI. Cortical thickness was measured using the surface based method. The topography of cortical thinning related to WMH was distributed in the frontal and perisylvian regions, which was similar to that of PWMH. In contrast, there were only small areas of cortical thinning inversely associated with DWMH, which were distributed in medial frontal and lingual gyrus. PWMH, but not DWMH, were associated with the frontal thinning and executive dysfunction; where both PWMH and frontal thinning were independently associated with executive dysfunction. Our results suggest that PWMH are associated with frontal thinning, which is further associated with frontal executive dysfunction.